What Is a Thyroid Releasing Hormone (TRH) Stimulation Test?

What to expect when undergoing this test

Lab technician with blood samples and medical chart
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A thyrotropin-releasing hormone (TRH) stimulation test is a diagnostic test that involves taking an intravenous (IV) dose of TRH to assess its effect on your thyroid hormones. This test can provide information that may be useful in distinguishing different types of thyroid problems. However, the TRH stimulation test is not considered safe and is not approved by the U.S. Food and Drug Administration (FDA) as a diagnostic test for patients.

As a result of these issues, it is used primarily as a research tool. The test also has limited availability as a diagnostic test for thyroid disease outside the United States.

Purpose of Test

Thyroid hormone production requires many steps. Your hypothalamus, located in your brain, monitors the conditions of your body and secretes thyrotropin-releasing hormone (TRH) when you need more thyroid hormones. TRH prompts your brain's pituitary gland to release thyroid stimulating hormone (TSH).

TSH stimulates the thyroid gland itself to make thyroid hormones, T4 and T3, which increase your body's metabolism to provide you with energy.

While symptoms that can arise when something goes amiss are generally owed to an underactive or overactive thyroid, there is a range of possible causes, and the right treatment depends on which one applies to you.

Low levels of T3 and T4 can be caused by:

  • A problem with your thyroid gland (primary hypothyroidism)
  • Your pituitary gland (secondary hypothyroidism)
  • Your hypothalamus (tertiary hypothyroidism)

(Secondary and tertiary hypothyroidism are both considered central hypothyroidism.)

The TRH stimulation test is primarily considered a tool for differentiating primary hypothyroidism from secondary or tertiary hypothyroidism when T3 and T4 levels are not enough to draw a confident conclusion.

Limitations

The TRH stimulation test usually triggers a rise in TSH, and the extent of the change may help identify secondary and tertiary hypothyroidism. However, the TSH response to the TRH stimulation test is not reliable, and the results do not usually provide more insight into the cause of thyroid disease than TSH, T4, and T3 levels.

Thyroid Function Tests and Normal Ranges

Risks and Contraindications

The rapid increase in thyroid hormone levels that can occur is the biggest concern with the TRH stimulation test, as this can cause increases or decreases in blood pressure or pulse, raising the risk of blood clots, stroke, transient ischemic attack (TIA), or seizures.

Other notable potential side effects of the test include:

  • Headaches
  • Lightheadedness
  • Dizziness
  • Excessive sweating
  • Abdominal discomfort
  • Nausea/vomiting
  • Women: Breast enlargement or leaking of milk/fluid from the breasts for several days

Contraindications

Women who are pregnant can experience excessive hormone fluctuations, as well as rapid changes in blood pressure that could endanger the developing baby.

If you have a pituitary tumor, stimulation with TRH can cause pituitary apoplexy, which is dangerous bleeding of the pituitary gland that may require emergency surgical intervention.

This test can also interfere with thyroid medications, and the side effects can be more severe if you take medications for adrenal disease.

The use of steroids, aspirin (acetylsalicylic acid) or medications used for Parkinson's disease can alter the results, making interpretation unreliable.

Before the Test

If you are set to have a TRH stimulation test done, this means that you are likely part of a research study, or that your thyroid hormone results are unusual enough for your doctors to request that you have this test.

Your doctor will discuss specific instructions, such as whether you should continue to take your usual medications before, during, and after the test. This depends on whether your blood pressure tends to fluctuate or to run too high or too low.

Timing

You should expect to devote a few hours to this test. You will have blood tests taken 30 and 60 minutes after receiving the injection. Additionally, your medical team may want to observe you for several hours after the test to watch for any medical complications. If you experience any complications, you can expect your recovery time to take hours or even days, as the medical team stabilizes you.

Location

Your test may take place in the hospital or in a doctor's office.

A TRH stimulation test is done in a medical facility where your vital signs (blood pressure, heartbeat, breathing rate) can be monitored closely.

What to Wear

You may be able to have this test while wearing your regular clothes, or you may be asked to change into an examination gown. Your injection is most likely going to be in a blood vessel in your arm, and your blood will probably be drawn from your arm as well, so it is best to wear clothes with sleeves that are easy to roll up so that your lower to mid-arm can be easily exposed.

Food and Drink

This test is meant to be performed in the morning after overnight fasting from food and drink.

Cost and Health Insurance

The TRH stimulation test is not approved for standard medical use. Given this, and that it is not commonly done, the cost is not easy to predict. If your doctor requested that you have this test due to exceptional circumstances, contact your health insurance provider to confirm the details of payment, whether you will be expected to pay a portion of the cost, and how much that portion is.

If you are having this test as part of a research study, it may be covered as part of the research protocol. Check with your medical team to verify.

Pros and Cons of Clinical Trials

What to Bring

When you arrive for the test, you should bring your order form, a form of identification, and documentation of any research protocol that you are part of. If your insurance company has approved the test, you should bring documentation of the approval, as well as your insurance card.

It is best to bring someone who can drive you home after the test.

During the test

At your test, you may see your doctor or another physician, and you will see a nurse or a phlebotomist (specialist in drawing blood) as well.

Pre-Test

You will need to check in, sign consent forms, and possibly consent to payment. Before the test begins, you may be hooked up to a blood pressure and pulse monitor so that you can be monitored continuously or at 15-minute intervals.

Throughout the Test

During this test, you will have one IV injection and your blood will be collected three times. You will begin your test by having a blood sample drawn for a baseline TSH.

A blood draw will usually be taken from a vein in your arm, and possibly from your hand. Because you will have your blood collected more than once, your nurse or phlebotomist may use both your right and left arms.

For each collection, the practitioner will find a vein, wrap an elastic band above the area where your blood will be drawn, clean the area, insert the needle, and collect the blood. You may feel a brief, sharp pain when the needle enters your arm, and you may experience mild discomfort while the needle is in place.

This should take about 30 seconds each time, after which the elastic band and the needle are removed, and the area is covered with a bandage or gauze.

Alternatively, you may have a temporary port placed, which is kept in place for the duration of the test so that you will not need multiple needle sticks. For this, you will have a needle inserted into a vein, just like with a standard blood draw. This needle is attached to a tube, creating an "entry point" that can be used every time a practitioner needs to access your vein. You may experience the same discomfort as with a regular blood collection.

After your first blood sample is collected to determine your baseline TSH, your nurse or phlebotomist will inject the TRH over a period of several minutes. Adults are given a standard amount, while the dose for children is calculated by weight.

You may experience the same brief, sharp pain and/or mild discomfort throughout the injection. When done, the injection site will be covered with a bandage.

It is the TRH injection that can cause side effects, which can begin immediately, or at any time within the first few days after the test. If you experience dizziness, headaches, palpitations, shortness of breath, or vision changes, you should report them to the medical team right away.

Two more blood samples will be taken to measure your TSH level 30 minutes after your TRH injection, and again 60 minutes after the injection.

Post Test

You may be examined by your doctor or nurse once the test is done, and, if you haven't already, you should report any symptoms that you have developed at any time throughout the test before you leave. If you are having the test as part of a research study, there may be a specific study protocol with respect to your checkup after the test.

After the Test

You may feel some side effects after your test. The response to this test is not easy to predict with certainty.

You may have delayed effects of thyroid hormone overstimulation lasting for days. And, after experiencing an increased thyroid response, you may actually have a resulting suppression of your thyroid hormones. These effects can begin days after the test and may last for a few more.

If you experience insomnia, hyper-alertness, unusual hunger, lack of energy, or a dry mouth, you can expect them to gradually improve and then resolve within a week.

When to Seek Urgent Care

If you experience dizziness, palpitations, vision changes, chest pain, vomiting, severe headaches, or convulsions, get urgent medical attention right away.

Interpreting Results

The results of the blood test may be available within a few hours after your test, or they may take a few days to be returned if your blood sample needs to be sent to another lab.

The key feature of the TRH stimulation test is the change in TSH level after the TRH injection.

  • Normal thyroid function: TSH rises by 2.0 μU/mL or more within 60 minutes.
  • Hyperthyroidism: TSH rises by less than 2.0 μU/mL within 60 minutes.
  • Primary Hypothyroidism: TSH rises by more than 2.0 μU/mL for most people who have primary hypothyroidism.
  • Secondary hypothyroidism: TSH rises by less than 2.0 μU/mL for about half of those with secondary hypothyroidism.
  • Tertiary hypothyroidism: TSH rises by less than 2.0 μU/mL for about 10 percent of those with tertiary hypothyroidism.

A low TSH with low T4 and T3 suggests central hypothyroidism, while high TSH with low T4 and T3 suggests primary hypothyroidism.


It is important to consider standard thyroid test values when interpreting these results. Because TSH, T4, and T3 levels can provide adequate insight into the cause of hypothyroidism in the majority of cases, the TRH stimulation test does not typically add a great deal of useful information.

Follow-Up

If you need to have your test repeated, you should wait at least one week for the effects of the injection to wear off. Generally, repeating the test is rarely indicated, and it should only be repeated if your diagnosis remains unclear.

If you are taking part in a research study, the protocol may require repeating the test. Consider this in advance before committing to be a participant.

A Word From Verywell

Given the lack of availability of the TRH stimulation test, its limited value, and the fact that it is not FDA approved, it is unlikely that you will need to have this test. However, if you are going to, it is best to familiarize yourself with all of the risks and side effects so you can make the most educated decision.

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